Winning on Objective Indicia of Non-Obviousness in an IPR
John Kong | March 11, 2022
Quanergy Systems, Inc.. v. Velodyne Lidar USA, Inc.
Opinion by: O’Malley, Newman, and Lourie
Decided on February 4, 2022
Summary:
The Federal Circuit affirmed the PTAB’s validity decisions in two IPRs for Velodyne’s patent on lidar, relying substantially on Velodyne’s objective evidence of non-obviousness. Quanergy’s appeal attacked the PTAB’s presumption of a nexus between Velodyne’s product and the claimed invention. In particular, Quanergy challenged the nexus presumption by arguing that there were unclaimed features that attributed to the significance of Velodyne’s products, instead of the claimed invention. The Federal Circuit found the PTAB’s reasoning for how each alleged unclaimed feature resulted directly from claim limitations – such that Velodyne’s products are essentially the claimed invention – were found to be both adequate and reasonable.
Procedural History:
Quanergy Systems, Inc. (Quanergy) challenged the validity of Velodyne Lidar USA, Inc. (Velodyne) U.S. Patent 7,969,558 in two inter partes review (IPR) proceedings before the Patent Trial and Appeal Board (PTAB) as being obvious. The PTAB sustained the validity of the ‘558 patent. The Federal Circuit affirmed the PTAB’s decision.
Background:
The ‘558 patent relates to a lidar-based 3-D point cloud measuring system, useful in autonomous vehicles. “Lidar” is an acronym for “Laser Imaging Detection and Ranging.” Lidar technology uses a pulse of light to measure distance to objects. Each pulse of light for measurement results in one “pixel” and a collection of pixels is called a “point cloud.” A 3-D point cloud may be achieved by making measurements with the light pulses in up-down directions, as well as in 360 degrees. Representative claim 1 is as follows:
A lidar-based 3-D point cloud system comprising:
a support structure;
a plurality of laser emitters supported by the support structure;
a plurality of avalanche photodiode detectors supported by the support structure; and
a rotary component configured to rotate the plurality of laser emitters and the plurality of avalanche photodiode detectors at a speed of at least 200 RPM.
Quanergy relied on a Mizuno reference that uses a “triangulation system” measuring the distance to an object by detecting light reflected from the object to image sensors. Quanergy also relied on a Berkovic reference that teaches the triangulation technique, as well as a time-of-flight sensing technique. To win on obviousness, Quanergy relied on a broad interpretation of “lidar” to encompass both triangulation systems and “pulsed time-of-flight (ToF) lidar.”
However, the PTAB construed “lidar” to mean pulsed time-of-flight lidar because the ‘558 specification exclusively focuses on pulsed time-of-flight lidar in which distance is measured by the “time” of travel (i.e., flight) of the laser pulse to and from an object. The PTAB also found that Mizuno does not address a time-of-flight lidar system. Instead, Mizuno’s triangulation system is a short-range measuring device. And, the PTAB held that the skilled artisan would not have had a reasonable expectation of success in modifying Mizuno’s device to use pulsed time-of-flight lidar because Quanergy’s expert did not explain how or why a skilled artisan would have had an expectation of success in overcoming the problems in implementing a pulsed time-of-flight sensor in a short range measurement system such as that of Mizuno’s. Indeed, the Berkovic reference was found to suggest that the accuracy of pulsed time-of-flight lidar measurements degrades in shorter ranges, such as in Mizuno’s system.
But, more importantly, the PTAB relied substantially on Velodyne’s objective evidence of non-obviousness, which “clearly outweighs any presumed showing of obviousness by Quanergy” even if Quanergy satisfied obviousness with respect to the first three of the four Graham v John Deere factors (i.e., (1) scope and content of the prior art, (2) difference between the prior art and the claims at issue, (3) level of ordinary skill in the pertinent art, and (4) any objective indicia of nonobviousness).
Decision:
As for the initial claim construction issue regarding “lidar,” the Federal Circuit agreed with the strength of the intrinsic record focusing exclusively on pulsed time-of-flight lidar, collecting time-of-flight measurements, and taking note of the specification’s boasted ability to “collect approximately 1 million time of flight (ToF) distance points per second, overcoming commercial point cloud systems inability to meet the demands of autonomous vehicle navigation. Indeed, the court found Quanergy’s arguments for a broader construction to be inconsistent with the specification and therefore unreasonable.
Quanergy also challenged the PTAB’s presumption of a nexus between the claimed invention and Velodyne’s evidence of an unresolved long-felt need, industry praise, and commercial success.
To accord substantial weight to Velodyne’s objective evidence, that evidence must have a “nexus” to the claims, i.e., there must be a “legally and factually sufficient connection” between the evidence and the patented invention.
The Federal Circuit may presume a nexus to exist “when the patentee shows that the asserted objective evidence is tied to a specific product and that product ‘embodies the claimed features, and is co-extensive with them.” This co-extensiveness does not require a patentee to prove perfect correspondence between the product and the patent claim. Instead, it is sufficient to demonstrate that “the product is essentially the claimed invention.” In this analysis, “the fact finder must consider the unclaimed features of the stated products to determine their level of significance and their impact on the correspondence between the claim and the products.” “Some unclaimed features ‘amount to nothing more than additional insignificant features,’ such that presuming nexus is still appropriate.” “Other unclaimed features, like a ‘critical’ unclaimed feature that is claimed by a different patent and that materially impacts the product’s functionality, indicate that the claim is not coextensive with the product.”
This presumption of a nexus is rebuttable. However, a patent challenger may not rebut the presumption of nexus with argument alone. The patent challenger may present evidence showing that the proffered objective evidence was “due to extraneous factors other than the patented invention” such as unclaimed features or external factors like improvements in marketing or superior workmanship.
Here, Quanergy argued that the PTAB failed to consider the issue of unclaimed features before presuming a nexus and failed to provide an adequate factual basis or reasoned explanation dismissing the unclaimed features argument. Quanergy argued that Velodyne’s evidence relies on unclaimed features, including high frame-rate, dense 3D point cloud with a wide field of view and collecting measurements in an outward facing lidar for 360 degree azimuth and 26 degree vertical arc. And, such unclaimed features are critical and materially impact the functionality of Velodyne’s products. Therefore, the requisite presumption of a nexus does not exist.
However, the court found that the PTAB considered, and adequately/reasonably did so, the unclaimed features arguments, reasonably finding that Veloydyne’s products embody the full scope of the claimed invention and that the claimed invention is not merely a subcomponent of those products. First, the PTAB credited Velodyne’s expert testimony providing a detailed analysis mapping claim 1 to description of Velodyne’s product literature. Second, the claims call for a 3-D point cloud and the density of the cloud and the 360 degree horizontal field of view (i.e., the ”unclaimed features”) “result directly” from the limitation for “[rotating] the plurality of laser emitters and the plurality of avalanche photodiode detectors at a speed of at least 200 RPM.” The “3-D” feature necessarily infers both horizontal and vertical fields of view. The PTAB also pointed to (1) contemporaneous news articles describing the long-felt need for a lidar sensor that could capture points rapidly in all directions and produce a sufficiently dense 3-D point cloud for autonomous navigation, (2) articles praising Velodyne as the top lidar producer and Velodyne’s products, and (3) financial information and articles reflecting Velodyne’s revenue and market share to show commercial success.
The court also found the PTAB’s analysis of those unclaimed features arguments to be commensurate with Quanergy’s presentation of the issue. Here, the court found Quanergy’s unclaimed features arguments to be merely skeletal, undeveloped arguments. In contrast, the PTAB’s explanation of how each alleged unclaimed feature results directly from claim limitations – such that Velodyne’s products are essentially the claimed invention – were found to be both adequate and reasonable.
Quanergy also presented new arguments (not previously presented to the PTAB) that, to obtain the dense 3-D point cloud, Velodyne’s products require the unclaimed critical features of (1) more than 2 laser emitters, (2) a high pulse rate, (3) vertical angular separation between pairs of emitters and detectors, and (4) a rotation speed significantly greater than 200 RPM. However, the court held that these new arguments, presented only on appeal, were forfeited.
Takeaways:
- This case is a good primer for how to best present or attack objective indicia of non-obviousness.
- One key to success for objective indicia of non-obviousness is expert testimony mapping claimed features to product literature and explaining how and why that description of the product is essentially the claimed invention. Other helpful evidence includes contemporaneous news articles about the long-felt need, praise for the subject product, and financial information/articles showing the company’s commercial success, presumably tied to the subject product.
- If unclaimed features are asserted to attack a presumption of nexus, expert testimony explaining how those alleged unclaimed features are direct results from claimed limitations, so as to side step the attack, is helpful.
- Skeletal arguments are insufficient. If making an unclaimed features argument, it is best to flesh it out before the PTAB in detail, otherwise it will be considered forfeited if newly presented on appeal.
CLAIMS ARE VIEWED AND UNDERSTOOD IN THE CONTEXT OF THE SPECIFICATION AND THE PROSECUTION HISTORY
Bo Xiao | March 7, 2022
Nature Simulation Systems Inc., v. Autodesk, Inc.
Before NEWMAN, LOURIE, and DYK, Circuit Judges. Opinion for the court filed by Circuit Judge NEWMAN. Dissenting opinion filed by Circuit Judge DYK.
Summary
The Federal Circuit ruled in a split decision that the United States District Court for the Northern District of California erred in invalidating Nature Simulation System’s patents as indefinite.
Background
NSS sued Autodesk for allegedly infringing US Patents No. 10,120,961 (“the ’961 patent”) and No. 10,109,105 (“the ’105 patent”). The ’961 patent is a continuation-in-part of the ’105 patent, and both are entitled “Method for Immediate Boolean Operations Using Geometric Facets” directed to a computer-implemented method for building three-dimensional geometric objects using boolean operation.
The district court held a claim construction (Markman) hearing and subsequently ruled the claims invalid on the ground of claim indefiniteness, 35 U.S.C. § 112(b). In the hearing, Autodesk presented an expert declaration to request the construction of eight claim terms. NSS argued that construction is not necessary and the challenged terms should receive their ordinary meaning in the field of technology. The district court did not construe the terms. The district court explained that a claim term is indefinite, as a matter of law, if there are any “unanswered questions” about the term. The decision of the district court was based on two of the challenged terms in clauses [2] and [3] of Claim 1:
1. A method that performs immediate Boolean operations using geometric facets of geometric objects
implemented in a computer system and operating with a computer, the method comprising:
[1] mapping rendering facets to extended triangles that contain neighbors;
[2] building intersection lines starting with and ending with searching for the first pair of triangles that hold a start point of an intersection line by detecting whether two minimum bounding boxes overlap and performing edge-triangle intersection calculations for locating an intersection point, then searching neighboring triangles of the last triangle pair that holds the last intersection point to extend the intersection line until the first intersection point is identical to the last intersection point of the intersection line ensuring that the intersection line gets closed or until all triangles are traversed;
[3] splitting each triangle through which an intersection line passes using modified Watson method, wherein the modified Watson method includes removing duplicate intersection points, identifying positions of end intersection points, and splitting portion of each triangle including an upper portion, a lower portion, and a middle portion;
[4] checking each triangle whether it is obscure or visible for Boolean operations or for surface trimming;
[5] regrouping facets in separate steps that includes copying triangles, deleting triangles, reversing the normal of each triangle of a geometric object, and merging reserved triangles to form one or more new extended triangle sets; and
[6] mapping extended triangles to rendering facets.
The two terms are “searching neighboring triangles of the last triangle pair that holds the last intersection point” and “modified Watson method.” The district court stated that even if the questions are answered in the specification, the definiteness requirement is not met if the questions are not answered in the claims. NSS argued that on the correct law the claims are not indefinite.
Discussion
The Federal Circuit cited the opinion in Nautilus and emphasized that the claims are viewed and understood in the context of the specification and the prosecution history, as the Court summarized in Nautilus (Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 909 (2014) ).
The district court held the claims indefinite based on the “unanswered questions” that were suggested by Autodesk’s expert, as stated in the Declaration:
¶ 27. [T]he claim language, standing alone, does not specify which of those neighboring, intersecting triangles should be used to identify additional intersection points. Nor does the claim specify (where there are multiple potential intersection points for a given pair of neighboring triangles) which of the multiple potential intersection points should be used to extend the intersection line. Thus, the claim language is indefinite.
The Federal Circuit states that the “unanswered questions” is an incorrect standard and specifically pointed out that “ ‘Claim language, standing alone’ is not the correct standard of law, and is contrary to uniform precedent.” The Federal Circuit found that the district court did not consider the information in the specification that was not included in the claims and the district court misperceived the function of patent claims.
The Federal Circuit also noted that the court did not discuss the Examiner’s Amendment. During the prosecution of the ‘961 patent, the examiner discussed with the inventor and later suggested an amendment in the Notice Of Allowance to clarify the disputed language. The examiner suggested amending claim 1 and then withdrew the rejection based on the amendment. The amendment includes the limitation of the term in clause [3] as follows:
[3] splitting each triangle through which an intersection line passes using modified Watson method, wherein the modified Watson method includes removing duplicate intersection points, identifying positions of end intersection points, and splitting portion of each triangle including an upper portion, a lower portion, and a middle portion;
The Federal Circuit noted that the district court did not discuss the Examiner’s Amendment and held that the claims are invalid since the questions raised by Autodesk’s expert were not answered. The Federal Circuit found that the district court fails to give proper weight to the prosecution history showing the resolution of indefiniteness by adding the designated technologic limitations to the claims. The Federal Circuit further explained that “[a]ctions by PTO examiners are entitled to appropriate deference as official agency actions, for the examiners are deemed to be experienced in the relevant technology as well as the statutory requirements for patentability.” The Federal Circuit stated that “[i]t is not disputed that the specification describes and enables practice of the claimed method, including the best mode. The claims, as amended during prosecution, were held by the examiner to distinguish the claimed method from the prior art and to define the scope of the patented subject matter.”
Judge Dyk dissented from the majority and opined that the district court had read the patent claims in light of the specification to determine if it would inform those skilled in the art about the scope of the invention with reasonable certainty, which is exactly what is required under Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 910 (2014). Judge Dyk also states that the majority simply does not address the problem that the limitations are “not describe[d]” in the patent, “ambiguous” and “unclear,” and “inconsistent with” Figure 13 and the accompanying text. In his view, the test for definiteness is whether the claims “inform those skilled in the art about the scope of the invention with reasonable certainty,” but the majority relied on the fact that these limitations were suggested by the patent examiner.
Takeaway
- Claims are viewed and understood in the context of the specification and the prosecution history.
- Patent claims must provide sufficient clarity to inform about the scope of the invention with reasonable certainty.
BREATHE EASIER, THE CAFC PROVIDES GUIDANCE ON CONSTRUING THE CLAIMED CONCENTRATION OF A STABILIZER IN PATENTS FOR AN ASTHMA DRUG
Andrew Melick | February 25, 2022
AstraZeneca v. Mylan Pharmaceuticals
Decided December 8, 2021
Taranto, Hughes, and Stoll. Opinion by Stoll. Dissent by Taranto
Summary:
AstraZeneca sued Mylan for infringement of its patents covering Symbicort pressurized metered-dose inhaler (pMDI) which is used for treating asthma. At issue in this case is how to construe the limitation “PVP K25 is present at a concentration of 0.001% w/w.” The district court construed the concentration using the ordinary standard scientific convention using only one significant figure to encompass the range from 0.0005% to 0.0014%. Based on this construction, Mylan stipulated to infringement. The district court then held a trial on validity and upheld the validity of the asserted claims. The CAFC affirmed the district court’s judgment of validity. But the CAFC disagreed with the construction of the concentration limitation. The CAFC held that the construction of the term should be narrower than the range provided by the ordinary meaning due to disclosures in the specification and arguments and amendments in the prosecution history. The CAFC construed the noted concentration of 0.001% to include the narrower range of 0.00095% to 0.00104%. Thus, the CAFC vacated the judgment of infringement and remanded for further proceedings on infringement.
Details:
The patents at issue in this case are U.S. Patent Nos. 7,759,328; 8,143,239; and 8,575,137 which cover the asthma inhaler Symbicort pMDI. A pMDI inhaler uses a propellant gas that is in liquid form under pressure in the pMDI device. When the inhaler is activated, the propellant causes the gas to come out as a spray making it easier to deliver the medication to the lower lungs. The representative claim is provided:
13. A pharmaceutical composition comprising
formoterol fumarate dihydrate, budesonide, HFA227, PVP K25, and PEG-1000,
wherein the formoterol fumarate dihydrate is present at a concentration of 0.09 mg/ml,
the budesonide is present at a concentration of 2 mg/ml,
the PVP K25 is present at a concentration of 0.001% w/w, and
the PEG-1000 is present at a concentration of 0.3% w/w.
Mylan appealed the district court’s stipulated judgment of infringement asserting that the district court erred in the construction of the concentration of PVP K25 of 0.001%. Mylan also appealed the district court judgement of nonobviousness.
The CAFC stated that as a matter of standard scientific convention, the noted concentration of 0.001% being expressed with only one significant digit would ordinarily encompass a range from 0.0005% to 0.0014%. AstraZeneca argued that this ordinary meaning controls absent lexicography or disclaimer. However, the CAFC stated that this is an acontextual construction that does not consider disclosures in the specification and arguments/amendments in the prosecution history. The CAFC stated that “[c]onsistent with Phillips, therefore, we must read the claims in view of both the written description and prosecution history.”
The CAFC stated that the testing evidence in the specification and prosecution history demonstrates that minor differences as small as ten thousandths of a percentage (four decimal places) in the concentration of PVP impact stability. The specification repeatedly describes formulations containing 0.001% PVP as providing the best suspension stability. This is also demonstrated in the data provided in the specification. The data includes formulations including PVP at concentrations of 0.0001%, 0.0005%, 0.001%, 0.01%, 0.03%, and 0.05%. The results show that the formulation containing 0.001% PVP was the most stable and that the formulation containing 0.0005% was one of the least stable formulations. The CAFC concluded that this data shows that PVP concentration of 0.001% is more stable than formulations with slight differences in PVP concentration (e.g., a concentration of 0.0005%, and that differences down to the ten-thousandth of a percentage (fourth decimal place) matters for stability.
In the prosecution history, the Applicant amended the claims to change ranges of the concentration to recite the exact concentration of PVP to 0.001% without using the qualifier “about,” and emphasized that 0.001% was critical to stability. The CAFC also stated that Applicant knew how to claim ranges and describe numbers with approximation using the term “about,” but the Applicant chose to claim the exact value. The CAFC concluded that this supports construing 0.001% narrowly, but that there should be some room for experimental error in the PVP concentration. The CAFC stated that the margin of error that is best supported by the intrinsic record is variations in the PVP concentration at the fourth decimal place (0.000095% to 0.000104%).
AstraZeneca argued that Mylan’s proposed construction is an attempt to limit the scope of the claims to the preferred embodiment. However, the CAFC stated that AstraZeneca’s proposed construction would read on two distinct formulations described in the specification (0.0005% PVP and 0.001% PVP), but the Applicant chose to claim only one of these formulations. The CAFC also stated that Applicant cancelled claims that included the 0.0005% PVP concentration and that this provides evidence that the formulations containing 0.0005% PVP are not within the scope of an asserted claim.
Regarding the nonobviousness determination by the district court, Mylan argued that the district court erred in finding that the prior art reference Rogueda taught away from the claimed invention. The CAFC citing Meiresonne v. Google, Inc., 849 F.3d 1379 (Fed Cir. 2017), stated that “a prior art reference is said to teach away from the claimed invention if a skilled artisan ‘upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken’ in the claim.”
The Rogueda reference included control formulations to compare with its novel formulations. Mylan relied on some of the control formulations as rendering the claims obvious. Rogueda disclosed that the novel formulations provided a “drastic” reduction in the amount of drug adhesion compared to the controls.
Mylan, citing Meiresonne, argued that the court’s precedent regarding “teaching away” is that a reference “that merely expresses a general preference for an alternative invention but does not criticize, discredit, or otherwise discourage investigation into the claimed invention does not teach away.” Mylan argued that Rogueda merely expresses a preference for the novel formulations over the control formulations citing a statement in the district court opinion that “Rogueda did not necessarily disparage the formulations in Controls 3 and 9.” However, AstraZeneca provided expert testimony stating that a skilled artisan looking at the adhesion results in Rogueda would conclude that the control formulations “were not suitable” and “clearly don’t work.” The district court credited the expert testimony that a skilled artisan would have known that the control formulations were unsuitable, and thus, discouraging investigation into these formulations, and concluded that Rogueda teaches away and does not render the claims obvious. The CAFC stated that there was no clear error in the district court’s determination and affirmed the validity of the claims.
Dissent
Judge Taranto dissented from the claim construction opinion. Judge Taranto stated that 0.001% should be construed to have its significant-figure meaning of 0.0005% to 0.0014% with the possibility of shrinking the lower end of the range to exclude the overlap area between the significant-figure interval of 0.001% (0.0005% to 0.0014%) and the significant-figure interval of 0.0005% (00045% to 0.00054%). Thus, if this exclusion is applied, the range would be 0.00055% to 0.0014%.
Judge Taranto takes the position that nothing in the specification or prosecution history warrants departing from the ordinary meaning. Judge Taranto pointed out that the specification, when referring to the formulations that were tested, states that several of the formulations were “considered excellent” and that the formulation with 0.001% PVP “gave the best suspension ability overall.” In the prosecution history, the Examiner stated the need for the Applicant to show criticality by showing unexpected results of a 0.001% concentration level compared to concentration levels “slightly greater or less” than 0.001% PVP. But it is unclear if the Examiner meant to include 0.0005% and other tested concentration levels tested within the meaning of “slightly greater or less.” The Examiner’s statement about criticality does not exclude 0.0005%.
Judge Taranto also stated that changing “0.001%” having one significant figure to “0.0010%” having two significant figures (as proposed by Mylan and adopted by the majority) requires rewriting the claim term, and that this rewriting is counter to the specification and prosecution history. The specification and prosecution history uniformly used only one significant figure when referring to PVP concentration. Just because four decimal places were used for some PVP concentrations does not mean that all concentration values should be read to express a degree of precision to four decimal places. The specification uses four decimal places to refer to the absolute concentration level in examples where this is unavoidable such as for 0.0001% and 0.0005%. However, absolute levels and degrees of precision are distinct.
Judge Taranto also addressed the fact that the range implied by 0.001% overlaps the range implied by 0.0005%. Judge Taranto stated that the overlap does not support adding an extra significant digit. Judge Taranto stated that “the most this overlap could possibly support would be an exclusion of the small range with the one significant-figure interval for which there is overlap resulting in the range of 0.00055% to 0.0014%. However, Judge Taranto pointed out that Mylan’s product is still within this narrower range, and thus, it is not necessary to decide whether the overlap-area exclusion is justified as a claim construction.
Comments
The majority appears to have been swayed by the fact that a formulation within the range of the ordinary meaning of the claimed concentration provided significantly different results. What is not clear is whether these different results, while not the best, could still be considered good. Judge Taranto pointed out that the specification stated that several of the tested formulations were considered excellent while the 0.001% was the best. When drafting and prosecuting patent applications, you need to be aware that your experimental data and amendments to the claims can be used to narrow the range afforded by the ordinary meaning of a certain value.
With regard to arguing non-obviousness due to a teaching away in the prior art, expert testimony can be critical and should be used to support your argument whether you are defending the validity of a patent or trying to invalidate.
REASONABLE-EXPECTATION-OF-SUCCESS REQUIREMENT CANNOT BE SATISFIED WHEN THERE IS NO EXPECTATION OF SUCCESS
Stephen G. Adrian | February 4, 2022
Teva Pharmaceuticals USA v. Corcept Therapeutics, Inc.
Decided December 7, 2021
Moore, Newman and Reyna (Opinion by Moore)
This precedential opinion illustrates the importance of preparing your expert for deposition. Although an expert declaration was effective in having a Post Grant Review instituted on claims 1-13 of U.S. Patent No. 10,195,214, the expert’s post-institution deposition testimony was instrumental in upholding the validity of the claims. This opinion not only addresses obviousness with respect to the reasonable expectation of success requirement, but also obviousness of ranges, a topic covered by Michael Caridi earlier this month in Indivior UK Ltd., v. Dr. Reddy’s Labs S.A., Dr. Reddy’s Labs, Inc.
Mifepristone was developed as an anti-progestin in the 1980s and was later discovered to likely inhibit the effect of cortisol on tissues, suggesting that it could be used to treat Cushing’s syndrome (a disease caused by excessive levels of cortisol). Corcept filed for a New Drug Application (NDA) for Korlym (a 300 mg mifepristone tablet) to control hyperglycemia secondary to hypercortisolism in certain patients with Cushing’s syndrome. The NDA application was approved with a few post marketing requirements, one including a drug-drug interaction clinical trial to determine a quantitative estimate of the change in exposure of mifepristone following co-administration of ketoconazole (a strong CYP3A inhibitor). A memorandum provided by the FDA explained that “[t]he degree of change in exposure of mifepristone when co-administered with strong CYP3A inhibitors is unknown. . .”.
In approving Corcept’s NDA, the FDA also approved the Korlym label recommending a dose of 300 mg once daily and allowing for increasing dosage in 300 mg increments to a maximum 1200 mg once daily. In addition, the label warned against using mifepristone with strong CYP3A inhibitors and limited the dose to 300 mg per day when used with strong CYP3A inhibitors.
Corcept conducted the drug-drug interaction study and collected data on co-administration of mifepristone with a strong CYP3A inhibitor and received the ‘214 patent.
Teva sought post-grant review after Corcept asserted the ‘214 patent in district court, arguing that the claims would have been obvious based on the Korlym label and the FDA memorandum, optionally in combination with FDA guidance on drug-drug interaction. Furthermore, Teva provided an expert declaration of Dr. Greenblatt opining that it was reasonably likely that 600 mg mifepristone would be well tolerated and therapeutically effective when co-administered with a strong CYP3A inhibitor.
The Patent Trial and Appeal Board (PTAB) found that Teva had failed to prove that claims 1-13 would have been obvious. The PTAB construed the claims to require safe administration of mifepristone, and that Teva failed to show that one of ordinary skill in the art would have had a reasonable expectation of success for safe co-administration of more than 300 mg mifepristone with a strong CYP3A inhibitor.
Teva asserted that the PTAB had committed two errors: (1) that the PTAB erred in requiring precise predictability rather than a reasonable expectation of success, and (2) that the PTAB erred when it found Teva had failed to prove the general working conditions (ranges) disclosed in the prior art encompassed the claimed invention. The CAFC did not agree.
1. Reasonable Expectation of Success
The reasonable expectation of success analysis must be tied to the scope of the claims.
Claim 1 is representative:
A method of treating Cushing’s syndrome in a patient who is taking an original once-daily dose of 1200 mg or 900 mg per day of mifepristone, comprising the steps of:
reducing the original once-daily dose to an adjusted once-daily dose of 600 mg mifepristone,
administering the adjusted once-daily dose of 600 mg mifepristone and a strongCYP3A inhibitor to the patient,
wherein said strong CYP3A inhibitor is selected from the group consisting of ketoconazole, itraconazole, nefazodone, ritonavir, nelfmavir, indinavir, boceprevir, clarithromycin, conivaptan, lopinavir, posaconazole, saquinavir, telaprevir, cobicistat, troleandomycin, tipranivir, paritaprevir, and voriconazole.
The claims require safe co-administration of a specific amount of mifepristone with a strong CYP3A inhibitor. Teva failed to establish that one would have reasonably expected co-administration of more than 300 mg mifepristone with a strong CPY3A inhibitor to be safe for treatment of Cushing’s syndrome. The PTAB went further to find that one of ordinary skill in the art would have had no expectation of success. Although not in the CAFC’s opinion, the deposition testimony of Teva’s expert (Dr. Greenblatt) was devastating.From the deposition:
[Patent Owner’s Counsel]: Well, okay. With all those assumptions built into this, was this — was the result set forth here that there was little to no increase in adverse events, was that result predictable?
[Dr. Greenblatt]: It’s — the result is neither predictable or unpredictable. It is what it is. It’s the study was done as mandated by the FDA to get at the truth, and here’s the outcome of the study.
[Patent Owner’s Counsel]: So a person of skill in the art would not have expected there to be no increase in adverse events?
[Dr. Greenblatt]: The study was done to, in part, to answer that question, not to address an expectation. I don’t believe that there would be any expectation. You don’t know what’s going to happen, which is why you do the study.
[Patent Owner’s Counsel]: So if the same testing had shown that a dose of 600 mg mifepristone could not be safely administered with ketoconazole, would that have been expected by a person of skill in the art?
. . .
[Dr. Greenblatt]: Yeah, the same answer. I don’t think there’s an expectation. You’re doing the study to find out what the result is to get the scientific truth.
The PTAB had discredited Dr. Greenblatt’s pre-institution testimony based on this post-institution testimony which unequivocally stated that one of ordinary skill would have no expectation as to whether 600 mg of mifepristone and ketoconazole would be safe. 2. Prior Art Range Precedence
Teva had asserted that the sole administration of mifepristone up to 1200 mg was an overlap in the range required by claim 1. This argument failed because the evidence of recorded only supported that the general working conditions for co-administration was shown to be 300 mg/day. As such, there was no overlap. Thus. The PTAB’s finding that the prior art ranges do not overlap was supported by substantial evidence.
Takeaways
- Make sure your expert is prepared.
- Obviousness based on the reasonable-expectation-of-success analysis must be tied to the scope of the claims.
- General working conditions in the prior art need to be analyzed with respect to the scope of the claims.
